EFFECT OF V1-VASOPRESSIN RECEPTOR BLOCKADE ON ARTERIAL-PRESSURE IN CONSCIOUS RATS WITH CIRRHOSIS AND ASCITES

Angiotensin II blockade with saralasin in human cirrhosis with ascites is associated with a significant reduction in arterial pressure, indicating that endogenous angiotensin II plays an important role in the maintenance of systemic hemodynamics in this condition. The aim of the current study was to investigate whether vasopressin also contributes to the maintenance of arterial pressure in cirrhosis with ascites. The study was performed using three groups of cirrhotic rats with ascites and three groups of control animals. The administration of d(CH2)5Tyr(Me)AVP, a selective antagonist of the vascular effect of vasopressin, to 10 cirrhotic rats induced a significant reduction in mean arterial pressure (from 94 ± 4 to 85 ± 4 mm Hg; P < 0.001) and a significant increase in plasma renin activity (from 24.3 ± 4.9 to 34.3 ± 5.9 ng/mL · h; P < 0.02) and plasma norepinephrine concentration (from 1474 ± 133 to 2433 ± 253 pg/mL; P < 0.01). Similar results were observed following saralasin administration in a second group of 5 cirrhotic rats [mean arterial pressure decreased from 97 ± 4 to 85 ± 5 mm Hg (P < 0.001); and plasma renin activity and norepinephrine concentration increased from 18.4 ± 5.8 to 40.3 ± 5.7 ng/mL · h (P < 0.02) and from 1383 ± 70 to 2312 ± 334 pg/mL (P < 0.05), respectively]. The simultaneous blockade of angiotensin II and vasopressin in a third group of cirrhotic rats resulted in a significantly greater reduction of mean arterial pressure (from 97 ± 6 to 74 ± 6 mm Hg; P < 0.05). No changes in arterial pressure were observed in the three groups of control rats. These findings indicate that endogenous vasopressin is as important as angiotensin II in the maintenance of arterial pressure in cirrhotic rats with ascites and support the contention that arterial hypotension is the initial event leading to the stimulation of the renin-angiotensin system and vasopressin in this animal model of cirrhosis. © 1991.